Thiono compounds with =P(S)- or -C(S)-linkages have widespread uses despite hazards of mutagenicity or carcinogenicity. These effects doubtless ensue from metabolic generation of highly reactive intermediates, but little is known about the chemical details. Our first aim will be to clarify the structure, stability, and reactions of such intermediates. With =P(S)-linkages, cytochrome P-450 is believed to produce a phosphoxathiiran that loses singlet sulfur, S(1D), which then inserts into -SH to give a hydrodisulfide, -SSH; 31p NMR has indeed afforded us novel evidence at -25 degrees C for intermediates (structure unknown) with per acids. To show S(1D), we have generated it photochemically and developed new traps for it. One of several promising traps we have found is a penicillamine derivative, of which the -SH is converted to -SSH (confirming feasibility of the biological insertion); a N-mesyl counterpart is expected to be more stable and thus more useful. Traps then will be used both to seek nonphotochemical sources of S(1D) and to determine whether S(1D) is expelled from intermediates. Studies of the reactions of S(1D) with biologically important moieties then are planned. With -C(S)-linkages, views will be studied that oxidation proceeds through a S-oxide to a S,S-dioxide, which then may react as an electrophile or via a carbenoid, and that sulfine-like and sulfene-like structures or SO may be involved. Our second aim will be to seek chemical reasons for the carcinogenicity and mutagenicity of thiono compounds, to assess relative potencies, and to develop means for predicting relative hazards. Our third aim, based on the fact that many anticancer drugs are carcinogenic and the hope that the converse may apply, is to supply thiono compounds to the National Cancer Institute for screening, in a search for novel classes of antineoplastic drugs. Significant basic contributions are anticipated to sulfur chemistry (e.g. vis-a-vis atomic sulfur, SO, thioamides and related heterocycles, hydrodisulfides, thiols, di- and polysulfides, sulfine- and sulfene-like species, sulfonamides), to the chemistry of pentavalent phosphorus and of small-ring heterocycles (phosphoxathiirans, oxathiirans), and to general organic chemistry (unusual carbenoids, peraminoalkenes).